Calcium Homeostasis Quiz

Calcium Homeostasis

• Calcium homeostasis is crucial for maintaining a stable calcium level in the body.
• Dietary calcium is the primary source, obtained through diet.
• It is a macromineral, that needs to be consumed in amounts greater than 100 mg/day.
• Stored in bone (98%), extracellular fluid (1%) and small amounts involved in signaling within cells.
• Essential for many body functions: Muscle contraction, nerve excitability, neurotransmitter and hormonal release, enzyme function and blood clotting.
• Normal extracellular calcium levels are tightly regulated between 2.2 - 2.6 mmol/L.
• The only "in" factor is dietary calcium intake.

Learning Outcomes

• Outline the factors affecting calcium homeostasis
• Describe Vitamin D metabolism
• Outline the role of PTH, PTHrP and calcitonin
• Describe bone turnover and different forms of metabolic bone disease
• Describe the clinical features of hypercalcemia and hypocalcemia.
• Outline calcium regulation mechanisms.

What is Calcium?

• Most abundant mineral in the human body.
• Essential for the body's functions.
• Key component of hydroxylapatite, forming bones and teeth.
• Acts as a reservoir for calcium and supports structural integrity.
• Small amounts used in cells for signaling.
• Disorders of phosphate and magnesium often coexist with calcium imbalances.

Essential Functions of Calcium in the Human Body

• Muscle contraction and nerve excitability: Regulates nerve impulse transmission.
• Neurotransmitter and hormonal release: Facilitates neurotransmitter release and hormone secretion.
• Enzyme function: Acts as a cofactor in several enzymes.
• Blood coagulation: Vital for blood clotting.
• Structural support: Provides strength to bones and teeth.
• Membrane integrity and permeability: Maintains cell membrane stability,.
• Plays a critical role in blood clotting and hormone and neurotransmitter secretion.

Calcium Regulation

• Dietary calcium intake (~200mg daily) and absorption by the small intestine. Active vitamin D is required.
• Blood Calcium Levels are tightly regulated between 2.2-2.6 mmol/L
• Bone acts as a reservoir, enabling calcium mobilization in response to other mechanisms failing.
• Kidneys filter and reabsorb calcium.
• Hormonal regulation: Parathyroid Hormone (PTH), Calcitriol (Vitamin D) and Calcitonin.
• Calcium is absorbed in the small intestine, with active transport requiring vitamin D dependent processes.
• PTH regulates calcium reabsorption/loss in the kidneys.
• Calcitonin promotes calcium deposition in bone.

Vitamin D - Calcitriol

• Lipid soluble vitamin or steroid hormone.
• Enhances calcium and phosphate absorption in intestines.
• Supports bone mineralization and resorption.
• Promotes renal calcium reabsorption in synergy with PTH.
• Ergocalciferol (D2) from plants. Cholecalciferol (D3) from animal sources.
• Produced in the skin, metabolized by liver and kidneys into active form 1,25-dihydroxyvitamin D (calcitriol).

Vitamin D - Calcitriol Synthesis

• 7-dehydrocholesterol is converted in the skin to vitamin D3 via UV light.
• Liver converts vitamin D3 into 25-hydroxyvitamin D.
• Kidneys convert 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D.

Calcium Regulation Hormone Levels

• Hypocalcaemia is associated with reduced calcium levels, triggering PTH increases & Vitamin D3. production causing mobilization of calcium from bone to increase extra cellular levels.
• Hypercalcaemia levels that are too high are moderated by increases in calcitonin.

Intestinal Calcium Absorption

• Two mechanisms are for calcium absorption (passive and active transport).
• Passive absorption throughout the small intestine, proportionally relating to the intraluminal calcium concentration; active transport is located mainly in the duodenum. It requires active vitamin D metabolites (1,25-dihydroxyvitamin D).

Vitamin D Receptor (VDR)

• Binding protein transports vitamin D in the blood.
• 1,25(OH)2D binds to intracellular vitamin D Receptor (VDR).
• VDR forms a heterodimer with RXR (Retinoid X Receptor).
• This complex binds to vitamin D Response Element (VDRE), directing transcription of genes in calcium homeostasis, cell proliferation, differentiation, and immune responses.

Importance of Calcium Measurement

• Reflects calcium homeostasis.
• Total calcium includes bound and free calcium.
• Ionized calcium is active calcium.
• Associated tests, (e.g., PTH, Vitamin D, phosphate) are important for monitoring calcium homeostasis.

Normal Calcium Homeostasis

• Absorption of calcium from the digestive tract, regulation of calcium in plasma and excretion of calcium by the kidneys are critical.
• The diagram illustrates the interplay of these key processes in maintaining calcium balance.

Factors affecting Calcium Homeostasis

• Dietary Intake & Urinary Loss: Calcium intake and renal function regulating urinary calcium loss.
• Plasma Hormones & Vitamins: PTH, calcitonin, and vitamin D influence intestinal calcium absorption levels.
• End-Organ Function: Activities in the intestines, kidneys and liver regulate calcium excretion and absorption levels.
• Plasma Factors: Calcium binds to albumin; low albumin reduces total calcium levels. Acid/Base Balance / Acidosis/ Alkalosis is a key influencing factor.

Hormones regulating calcium in the body: Parathyroid Hormone (PTH)

• 84 amino acid polypeptide produced by chief cells of the parathyroid gland.
• Increases blood calcium (Ca2+) levels.
• Bone, Kidney, Intestine are target organs.

Parathyroid Hormone (PTH)

• Calcium (Ca2+) and magnesium (Mg2+) in the kidneys increase renal reabsorption, decreasing urinary loss.
• Phosphate (HPO42-) decreases reabsorption, promoting phosphate excretion.
• Vitamin D activation stimulates 1-a-hydroxylase to convert 25-hydroxyvitamin D into the active form 1,25-dihydroxyvitamin D (calcitriol).- Gastrointestinal (GI) tract: PTH indirectly enhances calcium, phosphate and magnesium absorption via increased calcitriol levels. This process is critical for promoting intestinal calcium absorption when active vitamin D levels are high, supporting bone health.
• Bone: PTH promotes bone resorption through the stimulation of osteoclasts, releasing calcium and phosphate into the blood.
• Enhances the activity of osteoclasts and indirectly impacts osteoblast function, thereby controlling bone remodeling and regulating blood calcium levels.

Parathyroid Hormone-related Protein (PTHrP)-

• Crucial for calcium regulation distinct from PTH's primary effects
• Structurally related to PTH (140 vs 84 amino acids)
• Binds to the same receptor (PTH1R) as PTH, interacting with other receptors.
• Influences calcium and phosphate homeostasis, placental calcium transfer, development of mammary glands, smooth muscle function, and bone/cartilage.
• Overproduction associated with certain cancers causes hypercalcaemia (HHM), by mimicking PTH action.

Calcitonin

• Opposite action to PTH; lowers blood calcium levels.
• 32 amino acid polypeptide
• Secreted by C-cells of thyroid gland, stimulated by elevated calcium levels in the blood.
• Binds to calcitonin receptor on osteoclasts; inhibiting osteoclast activity, reducing bone resorption.
• Stimulates osteoblasts, increases bone formation.

Normal Calcium Homeostasis- Summary

• Illustrates a diagram of calcium homeostasis.
• Indicates absorption from the digestive tract, plasma regulation by soft tissues, calcium levels and bone calcium regulation and excretion.
• A key aspect is the coordination between various hormones(PTH, Calcitonin, and Vitamin D) and organs (intestines, kidneys, and bone) for effectively regulating calcium homeostasis.

Calcium Excretion

• Normal daily urinary excretion is <250 mg for women, <300 mg for men.
• Freely filtered by glomeruli.
• 60-70% is reabsorbed in the proximal tubule.
• Reabsorption occurs in other areas depending on hormone levels.
• Feces is a factor influencing calcium output.
• Factors influencing calcium excretion can include increased plasma calcium, Vitamin D, immobilization and corticosteroid use. Reduced rates occur with lowered plasma calcium, and kidney disease.

Cells Regulating Bone Turnover

• Osteoclasts: Break down and remove damaged bone, vital for repair.
• Osteoblasts: Secrete osteoid (unmineralized collagen matrix) to form bone; regulate osteoclast activity and promote bone formation.
• Osteocytes: Mature osteoblasts embedded in bone matrix; sensing mechanical stress and coordinating remodelling.

Importance of Calcium Measurement

• Measures calcium homeostasis via blood tests.
• Tests include total calcium (bound and free), ionized calcium (active form), along with levels of Phosphate, Vitamin D, and PTH to monitor the state of calcium homeostasis.

Rickets (Children)/Osteomalacia (Adults)

• Vitamin D deficiency leads to bone demineralization.
• Rickets involves soft, pliable bones, high fracture risk.
• Osteomalacia involves demineralization of existing bones, high fracture risk.
• Diagnosis includes X-rays, serum calcium, alkaline phosphatase, and phosphorus.
• Treatment is Cholecalciferol supplementation.

Osteoporosis

• Disorder of reduced bone matrix, low bone mass.
• Plasma calcium and phosphate levels are usually normal.
• Risk factors include age (especially women >50, men >70), hyperparathyroidism, deficiencies in calcium/vitamins, and prolonged use of glucocorticoids.
• Diagnosis involves fragility fractures and bone mineral density (DEXA) testing.
• Treatment options include exercise, reducing alcohol and smoking cessation, and medications like bisphosphonates, Denosumab, Teriparatide, romosozumab, and estrogen for bone metabolism to prevent progression.

Paget's Disease

• Accelerated bone remodeling, abnormal bone overgrowth.
• Symptoms include mixed lytic and sclerotic bone changes, increased osteoclastic activity, leading to abnormal new bone formation, pain, deformity, and fractures.
• Diagnosis includes X-rays, bone scintigraphy, MRI/CT, and elevated serum alkaline phosphatase measurements.
• Treated with bisphosphonates, or calcitonin for intolerance.

Clinical Features of Hypocalcemia

• Neuromuscular: Numbness, tingling, muscle cramps, spasms, Positive Chvostek's / Trousseau's sign, proximal myopathy.
• Bone: Bone pain and risk of fractures.
• CNS: Psychiatric disturbances, memory issues, seizures, and cataracts (long-term cases).

Clinical Features of Hypercalcemia

• CNS: Malaise, weakness, vomiting, psychiatric disturbances, confusion, coma.
• Renal: Polyuria, polydipsia, renal stones, nephrocalcinosis, kidney issues.
• Bone: Bone pain, constipation, duodenal ulceration.
• Cardiac: Dysrhythmias.

Test your understanding of calcium homeostasis and its importance in the body. This quiz covers dietary sources, metabolic functions, and the roles of various hormones in calcium regulation. You will also explore clinical features related to calcium imbalance such as hypercalcemia and hypocalcemia.